Food-derived bio-functional peptides for the management of hyperuricemia and associated mechanism

Hyperuricemia,a metabolic disorder related to uric acid metabolism dysregulation,has become a common metabolic disease worldwide,due to changes in lifestyle and dietary structure.In recent years,owing to their high activity and few adverse effects,food-derived active peptides used as functional foods against hyperuricemia have attracted increasing attention.This article aims to focus on the challenge associated with peptide-specific preparation methods development,functional components identification,action mechanism(s)clarification,and bioavailability improvement.The current review proposed recent advances in producing the food-derived peptides with high anti-hyperuricemia activity by protein source screening and matched enzymatic hydrolysis condition adjusting,increased the knowledge about strategies to search antihyperuricemia peptides with definite structure,and emphasized the necessity of combining computer-aided approaches and activity evaluations.In addition,novel action mechanism mediated by gut microbiota was discussed,providing different insights from classical mechanism.Moreover,considering that little attention was paid previously on the structure-activity relationships of anti-hyperuricemia peptides,we collected the sequences from published studies and make a preliminary summary about the structure-activity relationships,which in turn provided guides for enzymatic hydrolysis optimization and bioavailability improvement.Hopefully,this article could promote the development,application and commercialization of food-derived anti-hyperuricemia peptides in the future.

A novel strain of Levilactobacillus brevis PDD-5 isolated from salty vegetables has beneficial effects on hyperuricemia through anti-inflammation and improvement of kidney damage

Hyperuricemia is a metabolic disorder caused by abnormal purine metabolism,resulting in abnormally high serum uric acid.In this study,a novel Levilactobacillus brevis PDD-5 isolated from salty vegetables was verified with the function of alleviating hyperuricemia.The relevant effects of L.brevis PDD-5 in lowering uric acid were analyzed by in vitro and in vivo experiments.The results showed that the L.brevis PDD-5 has(68.86±15.46)%of inosine uptake capacity and(95.75±3.30)%of guanosine uptake capacity in vitro.Oral administration of L.brevis PDD-5 to hyperuricemia rats reduced uric acid,creatinine,and urea nitrogen in serum,as well as decreased inosine and guanosine levels in the intestinal contents of rats.Analysis of relevant markers in the kidney by ELISA kits revealed that L.brevis PDD-5 alleviated oxidative stress and inflammation.Moreover,the gene expression of uric acid transporter 1(URAT1)and glucose transporter 9(GLUT9)was down-regulated,and the gene expression of organic anion transporter 1(OAT1)was up-regulated after treatment with L.brevis PDD-5.Western blot analysis showed that L.brevis PDD-5 alleviated hyperuricemia-induced kidney injury through the NLRP3 pathway.The se findings suggest that L.brevis PDD-5 can lower uric acid,repair kidney damage,and also has the potential to prevent uric acid nephropathy.

Andrias davidianus bone peptides alleviates hyperuricemia-induced kidney damage in vitro and in vivo

Hyperuricemia(HUA)is a vital risk factor for chronic kidney diseases(CKD)and development of functional foods capable of protecting CKD is of importance.This paper aimed to explore the amelioration effects and mechanism of Andrias davidianus bone peptides(ADBP)on HUA-induced kidney damage.In the present study,we generated the standard ADBP which contained high hydrophobic amino acid and low molecular peptide contents.In vitro results found that ADBP protected uric acid(UA)-induced HK-2 cells from damage by modulating urate transporters and antioxidant defense.In vivo results indicated that ADBP effectively ameliorated renal injury in HUA-induced CKD mice,evidenced by a remarkable decrease in serum UA,creatinine and blood urea nitrogen,improving kidney UA excretion,antioxidant defense and histological kidney deterioration.Metabolomic analysis highlighted 14 metabolites that could be selected as potential biomarkers and attributed to the amelioration effects of ADBP on CKD mice kidney dysfunction.Intriguingly,ADBP restored the gut microbiome homeostasis in CKD mice,especially with respect to the elevated helpful microbial abundance,and the decreased harmful bacterial abundance.This study demonstrated that ADBP displayed great nephroprotective effects,and has great promise as a food or functional food ingredient for the prevention and treatment of HUA-induced CKD.

Lacticaseibacillus rhamnosus Fmb14 ameliorates hyperuricemia-induced hepatocyte pyroptosis via NLRP3 inflammasome cascade inhibition

Hyperuricemia is a high-risk factor for the development of gout and renal fibrosis,but the adverse effects of hyperuricemia on the liver have been seriously neglected.This research investigated the ameliorating effect of Lacticaseibacillus rhamnosus Fmb14 on hyperuricemia induced liver dysfunction both in vitro and in vivo.Cell free extracts of high dose L.rhamnosus Fmb14 treatment reduced the death rate of HepG2 cell lines from 24.1%to 14.9%by inhibiting NLRP3 recruitment,which was mainly activated by reactive oxygen species release and mitochondrial membrane potential disorder.In purine dietary induced hyperuricemia(PDIH)mice model,liver oedema and pyroptosis were ameliorated after L.rhamnosus Fmb14 administration through downregulating the expression levels of NLRP3,caspase-1 and gasdermin-D from 1.61 to 0.86,3.15 to 1.01 and 5.63 to 2.02,respectively.L.rhamnosus Fmb14 administration restored mitochondrial inner membrane protein(MPV17)and connexin 43 from 2.83 and 0.73 to 0.80 and 0.98 respectively in PDIH mice,indicating that dysbiosis of mitochondrial membrane potential was restored in liver.Intriguingly,PDIH pyroptosis stimulates the process of apoptosis,which leads to severe leakage of hepatocytes,and both of pyroptosis and apoptosis were decreased after L.rhamnosus Fmb14 treatment.Therefore,L.rhamnosus Fmb14 is a promising biological resource to maintain homeostasis of the liver in hyperuricemia and the prevention of subsequent complications.

Effect of dapagliflozin on uric acid in patients with chronic heart failure and hyperuricemia

BACKGROUND Patients with chronic heart failure(CHF)frequently develop hyperuricemia,an elevated serum uric acid level,associated with adverse outcomes.Dapagliflozin,a sodium-glucose cotransporter-2 inhibitor,demonstrates reduction in cardiovascular mortality and hospitalization in patients with CHF and ejection fraction(HFrEF),irrespective of diabetes.However,dapagliflozin’s effect on the uric acid levels in patients with CHF and hyperuricemia remain unclear.AIM To investigate the effects of dapagliflozin on uric acid levels in CHF patients with hyperuricemia.METHODS We conducted a randomized,double-blind,placebo-controlled trial in 200 patients with CHF and hyperuricemia,with HFrEF and serum uric acid levels≥7 mg/dL(≥416μmol/L).The participants were randomly assigned to receive a daily dose of 10 mg dapagliflozin or placebo for 24 months.The primary endpoint was the change in serum uric acid level from baseline to 24 months.Secondary endpoints included changes in left ventricular ejection fraction(LVEF),Nterminal pro-B-type natriuretic peptide(NT-proBNP),and quality of life(QoL)scores,as well as the incidence of cardiovascular death and hospitalization for heart failure.RESULTS At 24 months,dapagliflozin significantly reduced serum uric acid levels by 1.2 mg/dL(71μmol/L)compared with placebo(95%CI:-1.5 to-0.9;P<0.001).Dapagliflozin also significantly improved LVEF by 3.5%(95%CI:2.1-4.9;P<0.001),NT-proBNP by 25%(95%CI:18-32;P<0.001),and QoL scores by 10 points(95%CI:7-13;P<0.001)and reduced the risk of cardiovascular death and hospitalization for heart failure by 35%(95%CI:15–50;P=0.002)compared with the placebo.Adverse events were similar between the two groups,except for a higher rate of genital infections in the dapagliflozin group(10%vs 2%,P=0.01).CONCLUSION Dapagliflozin significantly lowered serum uric acid levels and improved the clinical outcomes in patients with CHF and hyperuricemia.Therefore,dapagliflozin may be a useful therapeutic option for this high-risk population.

Ameliorative effect of Lacticaseibacillus rhamnosus Fmb14 from Chinese yogurt on hyperuricemia

Hyperuricemia is a critical threat to human health,and a high inosine diet can increase the prevalence of it.Lacticaseibacillus rhamnosus Fmb14 was isolated from traditional fermented Chinese yogurt,and its inosine degradation rate reached 36.3%at 109 CFU/mL for 24 h.LC-MS analysis revealed that high concentrations of inosine could activate compensatory metabolic pathways of L.rhamnosus Fmb14 to catalyse inosine as an energy source and produce intracellular folic acid and riboflavin.The contents of folic acid and riboflavin were 6.0 and 4.3 fold increased after inosine treatment in the cell-free extracts(CFE).L.rhamnosus Fmb14 CFE treatment ameliorates hyperuricemia through xanthine oxidase(XOD)inhibition and ATP-binding cassette subfamily G member 2(ABCG2)promotion,both of which are responsible for uric acid(UA)synthesis and secretion in HepG2 and Caco2 cells,respectively.The in vivo results showed that the serum UA level decreased from 236.28 to 149.28μmol/L after 8 weeks of oral administration of L.rhamnosus Fmb14 in inosine-induced hyperuricemia model mice.Our results revealed that L.rhamnosus Fmb14 has a potential as a biological therapeutic agent in hyperuricemia prevention.

Chimonanthus nitens Oliv. leaves flavonoids alleviate hyperuricemia by regulating uric acid metabolism and intestinal homeostasis in mice

This study aimed to evaluate the alleviating effect of Chimonanthus nitens Oliv.leaves flavonoids(CLF)on hyperuricemia induced by potassium oxonate in mice.The results showed that CLF lowered the serum levels of uric acid(UA),creatinine and blood urea nitrogen,downregulated hepatic mRNA expressions of xanthine oxidase(XO),phosphate ribose pyrophosphate synthetase(PRPS)and adenosine deaminase(ADA)in hyperuricemia mice.In addition,CLF repaired renal injury by significantly down-regulating mRNA and protein expressions of renal UA reabsorption-related proteins and up-regulating the mRNA and protein expressions of UA secretory-related proteins.Finally,CLF inhibited UA synthesis and promoted UA excretion to alleviate hyperuricemia.Besides,CLF supplementation repaired the intestinal barrier function as demonstrated by significant increased mRNA levels of intestinal zonula occludens-1(ZO-1),Occludin,mucin 2(MUC2)and mucin 4(MUC4),as well as decreased mRNA levels of toll-like receptor 4(TLR4)and myeloid differentiation factor 88(MyD88)in mice.Further research showed that CLF treatment restored intestinal homeostasis mediated by improving the composition of gut microbiota and elevating the abundance of beneficial bacteria like Lactobacillus,Alistipes,Prevotellaceae_UCG-001 and Parasutterella.Overall,our findings revealed a novel function of CLF as a promising therapeutic candidate for the treatment of hyperuricemia.

Study on the effect of lowering uric acid and effect on the kidney of Poriae cutis in hyperuricemia mice

Objective:To explore the pharmacodynamic and renal protective effects of Poriae cutis extract on hyperuricemia(HUA)mice.Methods:The active components from the Poriae cutis were extracted with Alcohol solvent and aqueous solvent,HUA mice were established by hypoxanthine with potassium oxonate.Totally70 male Kunming mice were randomly divided into normal,model(500 mg/kg hypoxanthine+250 mg/kg potassium oxonate),Poriae cutis ethanol(PCE)and water extract(PCW)with high and low dose(388 mg/kg and 97mg/kg),benzbromarone(BEN)groups(7.5 mg/kg),all mice were administered with corresponding medication for 16 d.After the last administration,collected the 24 h urine volume,the urine uric acid(UUA)and urine creatinine(UCr)were determined.The morphological changes of the left kidney were viewed and the pathological changes in right kidneys were observed by hematoxylin-eosin(HE)staining.The serum contents of uric acid(SUA),creatinine(SCr)and urea nitrogen(BUN)were measured.Uric acid excretion index include fractional uric acid excretion(FEUA)and uric acid clearance rate(CUr)were calculated.The contents of OAT1,URAT1,GLUT9,TNF-αand IL-6 in the kidney were detected by ELISA.Results:PCE and PCW could increase UUA,UCr,FEUA,CUr and OAT1(P<0.05,P<0.01),reduce SUA,SCr,BUN,URAT1,GLUT9,TNF-αand IL-6(P<0.05,P<0.01).The pathological and morphological changes of kidneys in HUA mice were improved and the effect is better than BEN.Conclusion:Poriae cutis extractscould lower uric acid and possessed a protective effect on the kidney of mice with HUA,which was achieved by promoting uric acid excretion,regulating the expression of uric acid transporters and reducing the level of inflammatory factors.

Epidemiological characteristics of hyperuricemia in metabolic syndrome and its different components in the physical examination population

Objective:To explore the epidemiological characteristics of hyperuricemia(HUA)in the metabolic syndrome(MS)and its different components in the physical examination population.Methods:Subjects who underwent medical check-ups at a hospital health management center from June 2021 to March 2023 were included in the study.To analyze the prevalence of HUA in MS and its different components,further,stratify the study population by gender and assess the serum uric acid(SUA)levels and prevalence of HUA in people with different numbers of MS components and the combination of MS components with the highest prevalence of HUA in both sexes.Logistic regression was used to analyze the risk of HUA in people with different numbers of MS components.Result:A total of 66,520 individuals were enrolled in the study.SUA levels(t=-82.947,P<0.001)and HUA prevalence(χ^(2)=3421.632,P<0.001)were significantly higher in the MS group than in the Non-MS group.SUA levels and prevalence of HUA were significantly higher in abdominal obesity,hypertension,decreased HDL-C and evaluated TG than in normal subjects(P<0.001),while there were gender differences in SUA levels and HUA prevalence in diabetic patients,with significantly lower SUA levels and HUA prevalence in men with diabetes than in those with normal blood glucose,an opposite result in women.SUA levels and HUA prevalence gradually increased with the increasing number of MS components in women,whereas in men,such a trend was only observed in MS1-MS4.The combination of MS components with the highest prevalence of HUA was abdominal obesity+hypertension+decreased HDL-C+evaluated TG(54.35%)in men and abdominal obesity+hypertension+diabetes+decreased HDL-C+evaluated TG(41.46%)in women.Logistic regression analysis showed that after adjusting for gender,age and ethnicity,the risk of HUA increased with the number of MS components in women,while in men,the risk of HUA increased continuously from MS1-MS4.Further adjustment for BMI,elevated TC,elevated LDL-C,and coronary artery disease,the results remained consistent.Conclusion:MS and its components are risk factors for HUA in the physical examination population,with different combinations of MS components having different correlations with HUA,and the risk of developing HUA correlates with the number of abnormal MS components.

Meta-analysis of the impact of hyperuricemia on contrast agent-related acute kidney injury after percutaneous coronary intervention

Objective:To evaluate the impact of hyperuricemia on the occurrence of contrast agentrelated acute kidney injury after percutaneous coronary intervention.Methods:Retrieve PubMed,Embase,Cochrane Library,Web of Science,CNKI,Wanfang,and VIP databases,and publish articles on the correlation between hyperuricemia and contrast agent-related acute kidney damage after percutaneous coronary intervention from the establishment of the database to August 162023.Two researchers independently conducted literature screening and data extraction to evaluate the bias risk of inclusion in the study,and conducted metaanalysis using Review Manager 5.4 software.Results:A total of 12 articles were included,including 11676 patients.The meta-analysis results showed that compared with patients without hyperuricemia,patients with hyperuricemia had a higher risk of developing PC-AKI,with an incidence rate of 22.3%.Hyperuricemia was a risk factor for the occurrence of PCAKI(OR=2.03,95%CI:1.58-2.61);Patients with hyperuricemia have a higher risk of death after PC-AKI,with a mortality rate of 7.5%.Hyperuricemia is a risk factor for early death in PC-AKI patients(OR=2.33,95%CI:1.81-3.00);The probability of CRRT treatment after PCAKI in patients with hyperuricemia is higher,at 3.14%.Hyperuricemia is an influencing factor for CRRT treatment in PC-AKI patients(OR=7,95%CI:2.83-17.30).Conclusion:Existing research evidence suggests that the presence of hyperuricemia is an independent risk factor for the occurrence of PC-AKI,and it significantly increases the hospital mortality rate and the risk of renal replacement therapy in PC-AKI patients.

Structure-based multi-ligand molecular modeling to predict the synergistic effects of limonin and obacunone from Simiao pill against nitric oxide synthase 3 associated with hyperuricemia

Hyperuricemia(HUA)mainly occurs because of purine metabolism disorders.We recently proposed that limonin from Simiao pill may have therapeutic effects on nitric oxide synthase 3(NOS3)that is related to HUA.Concurrently,our previous work employed a new method,structure-based multi-ligand molecular modeling,to identify potential agents from a herbal formula that may produce synergistic effects and may have the potential to develop combination drugs.Therefore,we employed multi-ligand modeling to seek compounds with potential synergistic effects with limonin against NOS3.We obtained 403 multi-ligand docking results between 403 compounds and the limonin-NOS3 complex(average affinity–8.297 kcal/mol).Then we selected the top 10 highest binding affinity compounds for virtual pharmacokinetic and toxicity screening and we found that only obacunone passed all filters.We further subjected obacunone,bound to limonin and NOS3,to molecular dynamics simulations.We found that the NOS3-limonin-obacunone complex was more stable than the NOS3-limonin complex,based on the root mean square deviation of backbone Cαatoms and root mean square fluctuation,which suggests that synergistic effects may exist between limonin and obacunone.Further cell and animal experimental research is required to verify our results.

The mechanism of polyphenols in perilla against hyperuricemia using network pharmacology and molecular docking

To investigate the possible targets and mechanisms of polyphenols in perilla in the treatment of hyperuricemia(HUA)Batman-TCM,TCMSP,PubMed,and CNKI databases were used to obtain the main components of perilla and component-related targets.HUA targets were collected through GeneCards and OMIM online platforms.The HUA target and the perilla component target were crossed to obtain a common target.Protein interaction networks were constructed using the STRING database,and the compound-target-pathway network was constructed by Cytoscape software.The GO and KEGG enrichment analysis was performed using the DAVID database.Molecular docking was used to verify the results.Thirteen potential active components,101 component targets,901 HUA-related targets,and 36 common targets were screened out.Through network topology analysis,core targets such as TP53,TNF,CASP3,and PPARG and active components such as luteolin,β-carotene,cyanidin,catechin,and linolenic acid ethyl ester were obtained.The topology analysis of the“compound-target-pathway”network showed that the polyphenolic compounds luteolin,cyanidin,and catechin were the main active components of the perilla in the treatment of HUA.This study showed that the treatment of HUA with perilla had the characteristics of a multi-component,multi-target,and multi-signal pathway,which provided a scientific basis for further study on the molecular mechanism of the treatment of HUA with the potential active components of perilla.

Analysis of Clinical Characteristics of Patients with Different Types of Primary Hyperuricemia

Objective:This paper aims to study the clinical characteristics of patients with different types of primary hyperuricemia(HUA).Methods:Using a retrospective research method,200 patients with primary HUA in the hospital from June 2020 to January 2023 were selected as the research objects.Patients were grouped according to the detection results of 24-hour urinary uric acid excretion(UUE)and fractional excretion of uric acid(FEUA)(renal insufficiency type,renal overload type,mixed type,and other types).The general information of patients in the four groups(gender,age,body mass index,living habits,etc.),underlying diseases(hypertension,diabetes),blood test results[uric acid(UA),creatinine(Cre)],urine test results(24-hour urine UA,24-hour urine Cre)were summarized and the differences between the groups were analyzed.Results:The 200 cases of HUA patients were divided into 54.00%with renal insufficiency type,38.50%with mixed type,6.00%with renal overload type,and 1.50%with other types.The age of patients with mixed HUA was younger than that of patients with other types,renal overload type,and renal insufficiency type,and the difference was statistically significant(P<0.05).The UA level of patients with other types of HUA was lower than that of patients with mixed type HUA,and there was statistical significance(P<0.05).The Cre level of patients with mixed type HUA was lower than that of patients with renal insufficiency type and renal overload type,and the difference was statistically significant(P<0.05).The 24-hour urinary UA level in patients with renal insufficiency type HUA was lower than that in patients with renal overload type and mixed type HUA,and the difference was statistically significant(P<0.05).The 24-hour urinary Cre level of patients with other types of HUA was lower than that of patients with renal overload type and mixed HUA,the difference was statistically significant(P<0.05).The estimated glomerular filtration rate(eGFR)level of patients with other types of HUA was lower than that of patients with mixed type HUA,and the difference was statistically significant(P<0.05).There was no significant difference in the proportions of hypertension,diabetes,coronary heart disease,and urinary calculi among patients with renal insufficiency type,renal overload type,mixed type,and other types of HUA(P>0.05).Conclusion:The primary HUA patients are mainly of renal insufficiency type,followed by mixed type.There are significant differences in the clinical characteristics of patients with different types of HUA.Among them,patients with other types of HUA are the oldest and have the lowest uric acid levels.Patients with mixed HUA had the best renal function but the highest 24-hour urine creatinine level.This study can be used as a basis for rational selection of urate-lowering drugs for different HUA patients.

Hyperuricemia Accompanied with Changes in the Retinal Microcirculation in a Chinese High-risk Population for Diabetes

Objective To investigate the association of retinal vascular calibers with hyperuricemia in a middle‐aged and elderly population. Methods A cross‐sectional design was applied in this study and 869 participants aged ≥40 years from a high‐risk group for diabetes were recruited. All participants received the anthropometrical measurements and laboratory tests. Retinal arteriolar and venular caliber of the participants were measured with a semi‐automated system. Hyperuricemia was defined as a serum uric acid level 420 μmol/L in men and 360 μmol/L in women. Linear regression models were used to assess the association of hyperuricemia with retinal vascular calibers. These models were additionally adjusted for age, central obesity, hypertension, dyslipidemia, weekly activity, smoking status, and education. Results Among the 869 participants, 133 （15.3%） suffered from hyperuricemia. The crude mean serum uric acid level was 312.3 μmol/L （Standard Deviation 79.5）; mean concentration was 355.0 μmol/L （SD 75.5） in male participants, and 288.0 μmol/L （SD 71.1） in female participants （age‐adjusted difference 58.1 μmol/L, 95% Confidence Internal 48.5, 67.6）. After adjusting for additional covariates, male participants with hyperuricemia had 3.77 μm （95% CI ‐0.46, 8.00） smaller arteriolar caliber and 6.20 μm （95% CI 0.36, 12.04） larger venule than those without hyperuricemia; the corresponding numbers among female participants were 1.57 μm （95% CI ‐1.07, 4.21） for retinal arteriolar caliber and 2.28 μm （95% CI ‐1.72, 6.27） for retinal venular caliber. Conclusion Hyperuricemia was associated with smaller retinal arteriolar caliber and larger venular caliber mainly in male participants in this study.

Total Saponins from Dioscorea Septemloba Thunb Reduce Serum Uric Acid Levels in Rats with Hyperuricemia through OATP1A1 Up-regulation

The aim of this study is to evaluate the efficacy of total saponins of Dioscorea（TSD）, an extract of the Chinese herbal Bi Xie, on hyperuricemia and to elucidate the underlying mechanisms. The rat hyperuricemia model was established by administration of adenine. Thirty-two rats were randomly allocated into 4 groups： model group, low/high-dose TSD-treated groups, and allopurinol-treated group. Meanwhile, 8 rats were used as normal controls. Serum uric acid（UA）, blood urea nitrogen（BUN）, serum creatinine（Scr）, and organic anion transporting polypeptide 1A1（OATP1A1） levels were measured. Comparison between the model group and treatment（allopurinol and TSD） groups showed the serum UA levels were significantly decreased in treatment groups. TSD had similar effects to allopurinol. It was found that the OATP1A1 protein expression levels in treatment groups were higher than in model group and normal controls. And different from the allopurinol-treated groups, TSD-treated group had elevated OATP1A1 expression levels in the stomach, liver, small intestine and large intestine tissues. It was suggested that TSD may facilitate the excretion of UA and lower UA levels by up-regulating OATP1A1 expression.

Association between SLC2A9 Genetic Variants and Risk of Hyperuricemia in a Uygur Population

This study aimed to test the effects of five single nucleotide polymorphisms within SLC2A9 on uric acid level in a special ethnic population,the Uygurs in Xinjiang,China.According to our inclusion and exclusion criteria,Uygur adults from Xinjiang constituted the study population.There were 1053 Uygur adults with hyperuricemia and 1373 normal Uygur adults who served as controls.Five single nucleotide polymorphisms within SLC2A9(rs938557,rs7679916,rs7349721,rsl3101785,and rs 13137343)were selected with the HapMap dataset and TaqMan assays.We found that,in normouricemia group,rs938557 was significantly correlated with uric acid(β=11.39±3.74,P=0.0024)adjusting for age,gender and BMI;rs7679916 and rsl3137343 were marginally associated with uric acid concentration(β=5.77±3.O9,P=0.0626;p=-5.99±3.08,P=0.0520).In the hyperuricemia group,no SNP was found to possibly influence uric acid concentration.None of these SNPs showed significant association with hyperuricemia after controlling for age,gender and BMI.There were significant or marginal correlations between certain single nucleotide polymorphisms in the SLC2A9 region and uric acid concentration in Uygur normouricemia samples.In turn,some of these single nucleotide polymorphisms in SLC2A9 may increase the risk of hyperuricemia.

Effect of Eurycoma longifolia stem extract on uric acid excretion in hyperuricemia mice

OBJECTIVE Eurycoma longifolia is a tropical medicinal plant belonging to Simaroubaceae distributed in South East Asia.The aim of this study is to explore the effect and mechanism of E.longifolia stem 70%ethanol extract(EL)and its active com⁃poundson uric acid excretion.METHODS Potassium oxonate(PO)induced hyperuricemia rats and adenine-PO induced hyperuricemia mouse model were used to evaluate the effects of EL.Ultra Performance Liquid Chromatography was used to determine the levels of plasma or serum uric acid and creatinine.Hematoxylin-eosin staining was applied to observe kidney pathological changes,Western blot⁃ting was applied to detect protein expression levels of uric acid transporters.Effects of constituents on urate uptake were tested in hU⁃RAT1-expressing HEK293T cells.RESULTS EL significantly reduced serum and plasma uric acid levels at dosages of 100,200 and 400 mg·kg^-1 in hyperuricemia rats and mice,and increased the clearance rate of uric acid and creatinine,improved therenal pathological injury.The protein expression levels of urate reabsorption transporter 1(URAT1)and glucose transporter 9 were down-regulated while sodium-dependent phosphate transporter 1 and ATP-binding cassette transporter G2 were up-regulated in the kidney after EL treat⁃ment.The diterpenes(50μmol·L^-1)isolated from EL showed inhibitory effects on urate uptake in hURAT1-expressing HEK293T cells,and the effect of eurycomanol was further confirmed in vivo.CONCLUSION EL significantly reduced blood uric acid levels and prevented pathological changes of kidney in PO induced hyperuricemia animal model,improved renal urate transports.We partly clarified the mechanism was related to suppressing effect of URAT1 by diterpene in EL.This study is the first to demonstrate that EL plays a role in hyperuricemia by promoting renal uric acid excretion.

Prevalence of Hyperuricemia and Associated Factors in the Yi Farmers and Migrants of Southwestern China: A Cross-sectional Study

Hyperuricemia(HUA) is a common metabolic disease caused by increased formation or reduced excretion of uric acid. Although HUA does not cause direct damage to the body, it is closely related to the occurrence of various diseases, including gout,hypertension, diabetes mellitus, metabolic syndrome, and chronic kidney disease.

Status of Serum Uric Acid and Hyperuricemia among Adults in China:China Nutrition and Health Surveillance(2015)

Objective The purpose of this study was to determine the serum uric acid levels and the prevalence of hyperuricemia among Chinese adults in 2015 and compare the differences between urban and rural areas,as well as the differences between eastern,central,and western regions.Methods A national representative sample of 180,208 participants were included using a stratified,multistage,and random sampling method.The demographic characteristics and blood samples were collected to determine the serum uric acid levels and prevalence of hyperuricemia among subgroups using complicated sampling weight.A t-test or ANOVA was used for normally-distributed data.The Kruskal-Wallis rank test was used for skewed-distributed data.The Mantel-Haenszel chi-square test was used to compare the difference in categorical variables.Results The weighted mean uric acid level in Chinese adults was 310.4μmol/L(317.5μmol/L in urban areas and 302.9μmol/L in rural areas).The weighted average values of uric acid in eastern,central,and western China were 315.5μmol/L,303.5μmol/L,and 310.4μmol/L,respectively.The weighted prevalence of hyperuricemia in Chinese adults was 14.6%,with a prevalence of 16.5%in urban areas and12.5%in rural areas.The weighted prevalence of hyperuricemia in eastern,central,and western China was 16.0%,12.5%,and 14.8%,respectively.Conclusion The uric acid level in Chinese adults is relatively high.Effective actions are warranted to improve this metabolic abnormality.

Protective Effects of α-Lipoic Acid on Vascular Oxidative Stress in Rats with Hyperuricemia

The aim of the present study was to observe the protective effects of α-lipoic acid(ALA)on vascular injury in rats with hyperuricemia(HUA).The ALA treatment groups(10,30 and 90 mg/kg,respectively)were administered with ALA via gavage for 2 weeks.Subsequently,the levels of blood urea nitrogen(BUN),creatinine(CREA),uric acid(UA),total cholesterol(TC),high density lipoprotein-C(HDL-C)and low density lipoprotein-C(LDL-C)were measured;the activities of glutathione peroxidase(GSH-Px),catalase(CAT),malonaldehyde(MDA),superoxide dismutase(SOD)and xanthine oxidase(XOD)were also determined.The thoracic aorta of rats in each experimental group was observed under a light microscope;ultrastructural analysis was performed.SOD and CAT protein contents were investigated by Western blotting.The results revealed that:i)Compared with the model group,the levels of UA were decreased in the ALA groups and the levels of BUN,CREA,TC,and LDL-C decreased in the 30 and 90 mg/kg ALA groups(P<0.05);ii)compared with the model group,the activities of GSH-Px,SOD and XOD were increased and the levels of MDA were reduced in the 90 mg/kg ALA group (P<0.05);and iii)in the model and 10 mg/kg ALA groups,edema and shedding were observed in endothelial cells.Compared with the model and 10 mg/kg ALA groups,the 30 and 90 mg/kg ALA groups exhibited fewer swollen endothelial cells.In summary,the results of the present study indicated that HUA resulted in vascular oxidative stress injury and decreased the activity of antioxidative enzymes,which leads to endothelial cell damage and vascular lesions.ALA may serve as a therapeutic agent for the treatment of HUA-induced endothelial dysfunction.